William Placzek Ph.D.

William Placzek Ph.D.
Associate Professor

Associate Scientist (C), O'Neal Comprehensive Cancer Center , School of Medicine
Associate Scientist, Cancer Cell Biology , O'Neal Comprehensive Cancer Center
Scientist and Scientist (C), Center for Clinical and Translational Science (CCTS) , General Clinical Research Center
Associate Professor (P), Biochemistry & Molecular Genetics , Academic Joint Departments
Assistant Professor (S), Chemistry , College of Arts and Sciences

Overview

My research goal is to better understand the biochemical mechanisms that facilitate chemoresistance and employ NMR spectroscopy and synthetic peptides to identify novel therapeutic targets to suppress chemoresistance. To this end, my research focuses on two primary avenues: 1) Characterization of rBH3 motif mediated regulation of anti-apoptotic Bcl-2 family members; 2) Development of targeted inhibitors of the SUMOylation E2 enzyme, Ubc9. We also employ our expertise in peptide synthesis and assay design to develop peptide-based high-throughput screening assays that are amenable for small-molecule drug discovery and in the development of first-in-class peptide inhibitors that can be used to validate new therapeutic targets in cancer.

Selected Publications

Academic Article

Year	Title	Altmetric
2023	Phylogenetic analysis of the MCL1 BH3 binding groove and rBH3 sequence motifs in the p53 and INK4 protein families. PLoS One. 18. 2023
2021	The multiple mechanisms of MCL1 in the regulation of cell fate. Communications Biology. 4. 2021
2020	A cell-penetrating MARCKS mimetic selectively triggers cytolytic death in glioblastoma. Oncogene. 39:6961-6974. 2020
2020	MCL1 binds and negatively regulates the transcriptional function of tumor suppressor p73. Cell Death and Disease. 11. 2020
2020	The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synuclein. Journal of Biological Chemistry. 295:8005-8016. 2020
2020	Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synuclein 2020
2020	MCL1 binding to the reverse BH3 motif of P18INK4C couples cell survival to cell proliferation. Cell Death and Disease. 11. 2020
2020	Novel EGFR ectodomain mutations associated with ligand-independent activation and cetuximab resistance in head and neck cancer. PLoS One. 15. 2020
2019	Specific inhibition of DPY30 activity by ASH2L-derived peptides suppresses blood cancer cell growth. Experimental Cell Research. 382. 2019
2019	IgA1 hinge-region clustered glycan fidelity is established early during semi-ordered glycosylation by GalNAc-T2. Glycobiology. 29:543-556. 2019
2019	Regulating the bcl2 family to improve sensitivity to microtubule targeting agents. Cells. 8. 2019
2019	UBC9 Mutant Reveals the Impact of Protein Dynamics on Substrate Selectivity and SUMO Chain Linkages. Biochemistry. 58:621-632. 2019
2018	14-3-3 proteins reduce cell-to-cell transfer and propagation of pathogenic α-synuclein 2018
2018	PTBP1 enhances miR-101-guided AGO2 targeting to MCL1 and promotes miR-101-induced apoptosis article. Cell Death and Disease. 9. 2018
2018	Post-transcriptional regulation of anti-apoptotic BCL2 family members. International Journal of Molecular Sciences. 19. 2018
2018	Serum galactose-deficient-IgA1 and IgG autoantibodies correlate in patients with IgA nephropathy. PLoS One. 13. 2018
2016	PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics. Cell Death and Differentiation. 23:1681-1690. 2016
2013	Erratum to The E3Ubiquitin Ligase Siah2 Contributes to Castration-Resistant Prostate Cancer by Regulation of Androgen Receptor Transcriptional Activity [Cancer Cell 23, (2013) 332-346]. Cancer Cell. 23:853. 2013
2013	The E3 ubiquitin ligase siah2 contributes to castration-resistant prostate cancer by regulation of androgen receptor transcriptional activity. Cancer Cell. 23:332-346. 2013
2012	Novel targeted system to deliver chemotherapeutic drugs to EphA2-expressing cancer cells. Journal of Medicinal Chemistry. 55:2427-2436. 2012
2012	Sabutoclax, a Mcl-1 antagonist, inhibits tumorigenesis in transgenic mouse and human xenograft models of prostate cancer. Neoplasia. 14:656-665. 2012
2011	An optically pure apogossypolone derivative as potent pan-active inhibitor of anti-apoptotic Bcl-2 family proteins. Frontiers in Oncology. 1. 2011
2011	Identification of a novel Mcl-1 protein binding motif. Journal of Biological Chemistry. 286:39829-39835. 2011
2010	Synthesis and biological evaluation of apogossypolone derivatives as pan-active inhibitors of antiapoptotic B-cell lymphoma/leukemia-2 (Bcl-2) family proteins. Journal of Medicinal Chemistry. 53:8000-8011. 2010
2010	BI-97C1, an optically pure apogossypol derivative as pan-active inhibitor of antiapoptotic B-cell lymphoma/Leukemia-2 (Bcl-2) family proteins. Journal of Medicinal Chemistry. 53:4166-4176. 2010
2010	A survey of the anti-apoptotic Bcl-2 subfamily expression in cancer types provides a platform to predict the efficacy of Bcl-2 antagonists in cancer therapy. Cell Death and Disease. 1. 2010
2007	Cold-adaptation in Sea-water-borne Signal Proteins: Sequence and NMR Structure of the Pheromone En-6 from the Antarctic Ciliate Euplotes nobilii. Journal of Molecular Biology. 372:277-286. 2007
2007	Cold-adapted signal proteins: NMR structures of pheromones from the antarctic ciliate Euplotes nobilii. IUBMB Life. 59:578-585. 2007
2007	NMR Solution Structure of the Pheromone En-1 2007
2007	NMR Structure and Functional Characterization of a Human Cancer-related Nucleoside Triphosphatase. Journal of Molecular Biology. 367:788-801. 2007
2006	NMR assignment of a human cancer-related nucleoside triphosphatase [57]. Journal of Biomolecular NMR. 36:59. 2006
2006	Solution structures of the putative anti-σ-factor antagonist TM1442 from Thermotoga maritima in the free and phosphorylated states. Magnetic Resonance in Chemistry. 44. 2006
2005	Volatile anesthetics bind rat synaptic snare proteins. Anesthesiology. 103:768-778. 2005
2002	Volatile Anesthetics Bind to Synaptic SNARE Proteins and the SNARE Complex. Anesthesiology. 96:a813. 2002

Research Overview

Current projects being pursued in the lab are:
1. Characterizing the impact that reverse BH3 (rBH3)-containing proteins have on regulation of the anti-apoptotic Bcl-2 family proteins, especially MCL-1.

2. Determining the post-transcriptional regulators of the anti-apoptotic Bcl-2 family protein MCL-1.

3. Utilizing mutants of the SUMO E2 ligase, Ubc9, to study the structural determinants of SUMO target selection.

4. Developing high-throughput screening assays for use in anti-cancer therapeutic development.

Education And Training

Sanford-Burnham Medical Research Institute, Postdoctoral Fellowship

Doctor of Philosophy in Molecular Biology, The Scripps Research Institute 2007

Full Name

William Placzek